Iontophoresis is gaining increased acceptance as an effective method for application of ionic agents or ionic drugs through the skin of an animal. Iontophoresis can be defined as the electrically driven application of drugs or medications, in their ionic form, to the surface tissues of an animal. The application of electric current causes migration of ions into the tissue wherein such migration is proportional to the quantity of current applied through the iontophoretic system. Skin irritation can occur during iontophoretic drug delivery. Efforts to minimize irritation have been directed to regulating the level of current, improving the electrical connection of the electrode with the skin and reducing the hydrolysis of water in the ionic medication. Irritation of the skin may be subjective wherein the iontophoretic electrode delivers so much power that it causes extreme discomfort to the patient. There are also objective indicia of irritation such as petechia, erythemia and edema. Occurrence of such forms of irritation is discussed by Nancy A. Monteiro-Riviere in a paper presented in Fundamental Applied Technology, entitled "Altered Epidermal Morphology Secondary to Lidocaine Iontophoresis: In Vivo and In Vitro Studies in Porcaine Skin", Vol. 15, pages 174-185 (1990).
Numerous prior art references attempt to teach iontophoretic devices which attempt to avoid irritation and/or tissue damage. U.S. Pat. No. 4,292,968 to Ellis discloses an apparatus for delivering constant current during ion therapy (iontophoresis) which will abruptly switch to delivering constant voltage when the voltage across the electrodes reaches a predetermined level. U.S. Pat. No. 4,725,263 to McNichols et al. teaches a programmable constant current source transdermal drug delivery system wherein the current level can be adjusted or preset by trimming a circuit board in the apparatus.
U.S. Pat. No. 4,141,359 to Jacobsen et al. teaches an epidermal iontophoresis device which is capable of maintaining a constant current through the epidermal tissue. To prevent excessive voltage build-up and the accompanying dangers of shock and burns, a comparative circuit monitors current flow and voltage across the electrodes and automatically triggers and SCR shut down circuit when impedance readings are outside of predetermined limits.
U.S. Pat. No. 4,211,222 to Tapper teaches an iontophoretic burn protection method. Tapper teaches the use of an electrically conductive porous intervener having a thickness which is large in relation to the thickness of the skin. This intervener is interposed between a first electrode and the skin. Tapper also teaches that pain and tingling due to the passage of electric current can be reduced by increasing the area of the electrode delivering the drug. U.S. Pat. No. 4,164,226 to Tapper teaches iontophoretic burn-protection electrode structures wherein one electrode of an iontophoretic system has a porous material of a thickness in excess of 3 millimeters interposed between the electrode and the skin.
U.S. Pat. No. 4,764,164 to Sasaki teaches an iontophoresis device which includes an electric source including a pulse generator. The device has a circuit for discharging the charges accumulated in the electrodes during each intermission period of therapeutic pulses generated by the pulse generator. Sasaki teaches that the device can be easily applied to the human skin, without causing undesirable irritation in the skin, and especially without causing burns and rubefaction in the skin.
Although the prior art is replete with devices for reducing skin irritation and skin damage, the prior art efforts appear to focus on the device itself. Devices running on lower voltages, devices having intermediate pads between the electrodes and the skin, devices producing pulsating current, and devices having large electrode areas to reduce current concentration all approach the problem from a device perspective. The prior art has not attempted to understand the resistivity of the skin and develop a system that can take advantage of the natural properties of the skin in order to optimize the iontophoretic delivery while minimizing irritation and skin damages.